This serial-sacrifice study delineates the morphogenesis of pancreatic adenocarcinoma in the Syrian golden hamster, induced by 2,2'-dihydroxy-di-n-propyl-nitrosamine (DIPN), a model recently introduced by Pour et al. Fifty-two male out-bred hamsters, age 8 weeks, received weekly subcutaneous injections of DIPN (250 mg. per kg of body weight) suspended in olive oil. Control animals received only olive oil. One hour after an intraperitoneal injection of H3-TdR (3 microcuries per gm. of body weight), groups of four test and one control animal were sacrificed at 0,1,2,5,10,12,15,17,20,22,26, and 31 weeks. The pancreas was examined by high-resolution light (1 micron sections) and transmission electron microscopy. By 72 hours, all major pancreatic cell types showed a marked swelling and proliferation of smooth endoplasmic reticulum. Proliferation and hypertrophy of intra- and interlobular duct cells then occur and by 10 weeks multicentric foci of ductal cystic and papillary cystic hyperplasia are present; autoradiograms show an increased number of H3-TdR-labeled cells in these areas. There is progression to cyst-and papillary cystadenomas and intraductal and invasive ductal carcinomas, accompanied by marked atrophy of pancreatic actini, inflammation, and fibrosis.